Abdominal aortic aneurysm (AAA) is characterized by chronic aortic wall inflammation and loss of matrix components. Proinflammatory cytokines such as tumour necrosis factor-alpha (TNF-alpha) are thought to be involved in this inflammatory process and, therefore, to play an important role in the pathogenesis of human AAA. TNF-alpha-converting enzyme (TACE) has recently been purified and cloned as a disintegrin and metalloproteinase that converts TNF-alpha precursor into its mature form. The aim of the present study was to determine whether TNF-alpha and TACE were expressed and localized in aortic tissues in human AAA. Infrarenal aortic tissues were obtained from AAA patients (n=19) undergoing elective aneurysm reconstruction and from autopsy cases without cardiovascular disorders as normal controls (n=5). Internal thoracic artery samples were also obtained from patients with coronary artery disease undergoing coronary artery bypass grafting to represent biopsied conduit vessels (n=5). The AAA specimens were taken from the mid-portion of the aneurysm and from the longitudinal transition zone between the non-dilated aorta and the proximal aspect of the aneurysm. TNF-alpha and TACE mRNA levels were determined by real-time quantitative reverse transcriptase-PCR. Expression levels of both TNF-alpha mRNA and TACE mRNA were significantly greater in the transition zone than in the mid-portion (both P<0.05). Expression levels of both forms of mRNA were significantly higher in AAA samples than in control aortas or atherosclerotic arteries. There was a significant correlation between the expression of TNF-alpha mRNA with that of TACE mRNA in AAA (r=0.54, P<0.005). Immunostaining was positive for both TNF-alpha and TACE in CD68-positive macrophages in the media and adventitia obtained from the transition zone in AAA, whereas neither TNF-alpha nor TACE was expressed in control vessels. In conclusion, the concomitant activation and localization of TNF-alpha and TACE in the media and adventitia of the transition zone in human AAA underlines the importance of this system in the pathogenesis of this disorder.

This study has shown that increased myocardial TACE expression is associated with elevated myocardial TNF-alpha expression in both mRNA and protein levels in clinically advanced DCM.

These findings indicate that the expression of TNF-alpha and TACE may have important implications in the pathogenesis of myocarditis and may influence advanced cardiac dysfunction in myocarditis.

The pathway of tissue aldosterone production may exist in the heart, and may be an important contributory factor to myocardial fibrosis and cardiac remodelling in the failing heart. CYP11B2 (aldosterone synthase) catalyses the final step of aldosterone production. The aim of the present study was to determine whether CYP11B2 and CYP11B1 (11beta-hydroxylase) are expressed in myocardial tissues, and whether these enzymes contribute to collagen accumulation and myocardial dysfunction in the failing human heart. Endomyocardial tissues were obtained from 23 patients with chronic heart failure (CHF) and 10 controls. CYP11B2 and CYP11B1 mRNA levels were measured by real-time quantitative reverse transcriptase-PCR. The myocardial collagen volume fraction (CVF) was determined by digital planimetry. CYP11B2 mRNA expression was greater in the CHF group than in the controls (P<0.05), while CYP11B1 mRNA was barely expressed in either group. There was a positive correlation between CYP11B2 mRNA levels and CVF (r=0.64, P=0.001). CYP11B2 mRNA was particularly highly expressed in subgroups of CHF patients with a large left ventricular end-systolic diameter (>55 mm) or a low left ventricular ejection fraction (<30%). CYP11B2 mRNA expression and CVF were lower in a CHF subgroup treated with a combination of spironolactone and angiotensin-converting enzyme inhibitors (ACEIs) than in a subgroup not treated with these drugs. In conclusion, this study has shown that increased myocardial expression of CYP11B2 mRNA is associated with increased myocardial fibrosis and with the severity of left ventricular dysfunction in human CHF. In addition, CYP11B2 expression and cardiac fibrosis are found to be decreased in CHF patients on drug therapy comprising spironolactone combined with ACEIs.

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Aims/Methods: To investigate whether smoking affects the serum level of leptin, 708 male workers aged 25–65 years old were cross-sectionally surveyed. Results: Multiple regression analysis indicated that among the various parameters examined, the level of leptin was positively associated with the body mass index and the levels of insulin, total cholesterol and uric acid, and was inversely associated with physical activity and the level of creatinine. The partial correlation coefficient of leptin was highest against the body mass index (r = 0.40), followed by insulin (0.29) and physical activity (–0.14), after adjustment for other leptin-related variables. However, no association was observed between the level of leptin and smoking (0.05), alcohol consumption (0.09) or age (0.09). Conclusions: The findings suggest that among life-style habits, physical activity, but not smoking or alcohol consumption, significantly affects the serum level of leptin in Japanese men.

No abstract

A 34-year-old female farmer suffered from localized cutaneous mucormycosis for 17 years. At the first admission, the lesion was a dull red plaque, about 7 x 9 cm in size with ulcerations, surrounded by some nodules on the dorsum of her right hand. General examination did not reveal abnormal findings except the skin lesion. Direct examination of skin scrapings in 10% KOH revealed broad, sparsely septate, branching hyphae. Histopathology showed many intradermal granulomata and microabscesses as well as mycelial elements comprising broad, distorted, ribbon-like strands. Some of them were phagocytized by multi-nucleated giant cells. Cultures revealed rapidly growing yellow colonies on Sabouraud dextrose agar medium at 25 degrees C. Sporangiophores branched in sympodia and the sporangia were globose, 35-60 microns in diameter. Their walls were deliquescent, but some of them were rather persistent. Columellae were mostly globose, 12-17 microns in diameter, up to 35 microns with collars. Sporangiospores were mainly ellipsoidal, 1.5-2.5 x 3-5 microns in size, but sometimes highly variable in size and shape. The maximum growth temperature of the isolate was 37 degrees C. The pathogenic organism isolated was tentatively identified as Mucor lusitanicus, which, as far as we know, has not been reported as a causative agent of cutaneous mucormycosis.